ASIC1a contributes to the epithelial-mesenchymal transformation of breast cancer by activating the Ca2+ /ß-catenin pathway.

Breast cancer is the most common cancer in the world, with metastasis being one of the leading causes of death among patients. The acidic environment of breast cancer tissue promotes tumor cell invasion and migration by inducing epithelial-mesenchymal transformation (EMT) in tumor cells, but the exact mechanisms are not yet fully understood. This study investigated the expression of acid-sensitive ion channel 1a (ASIC1a) in breast cancer tissue samples and explored the mechanisms by which ASIC1a mediates the promotion of EMT in breast cancer cells in an acidic microenvironment through in vivo and in vitro experiments. The results showed that first, the expression of ASIC1a was significantly upregulated in breast cancer tissue and was correlated with the TNM (tumor node metastasis) staging of breast cancer. Furthermore, ASIC1a expression was higher in tumors with lymph node metastasis than in those without. Second, the acidic microenvironment promoted [Ca2+ ]i influx via ASIC1a activation and regulated the expression of ß-catenin, Vimentin, and E-cadherin, thus promoting EMT in breast cancer cells. Inhibition of ASIC1a activation with PcTx-1 could suppress EMT in breast cancer cells. Finally, in vivo studies also showed that inhibition of ASIC1a could reduce breast cancer metastasis, invasion, and EMT. This study suggests that ASIC1a expression is associated with breast cancer staging and metastasis. Therefore, ASIC1a may become a new breast cancer biomarker, and the elucidation of the mechanism by which ASIC1a promotes EMT in breast cancer under acidic microenvironments provides evidence for the use of ASIC1a as a molecular target for breast cancer treatment.

Identification of the Shared Gene Signatures and Biological Mechanisms in Hyperplastic Enlarged Lobular Units and Breast Cancer.

Breast cancer is a common cancer worldwide. Hyperplastic enlarged lobular units (HELUs) are common changes in the breasts of adult women. HELUs may be closely related to the occurrence and development of breast cancer. In this study, genes that are commonly contained in the expression profiles of the genomes of the two diseases and have significant differences in expression before and after the respective diseases were identified. Various enrichment analyses were performed according to the expression levels of these differentially expressed genes. Furthermore, LASSO regression analysis was performed on the differentially expressed genes to identify genes significantly related to survival. The optimal risk model for the survival of patients with breast cancer was established, and the accuracy of the model was verified on multiple data sets. A gene combination containing 17 genes was ultimately determined to be an independent prognostic factor. Kaplan‒Meier survival analysis demonstrated the good performance of this risk model. The study found that Shared Gene Signatures and Biological Mechanisms in Hyperplastic Enlarged Lobular Units and Breast Cancer, screened 17 important Shared Gene Signatures of Hyperplastic Enlarged Lobular Units which are closely related to the survival of breast cancer patients through machine learning, and established a prognosis model with high-accuracy, which is worthy of further exploration.

Homology modeling and molecular docking simulation of martentoxin as a specific inhibitor of the BK channel.

Background: Large conductance calcium-activated potassium channel (BK channel) is gated by both voltage and calcium ions and is widely distributed in excitable and nonexcitable cells. BK channel plays an important role in epilepsy and other diseases, but BK channel subtype-specific drugs are still extremely rare. Martentoxin was previously isolated from the venom of members of Scorpionidae and shown to be composed of 37 amino acids. Research has shown that the pharmacological selectivity of martentoxin to the BK channel is higher than that to other potassium channels. Therefore, it is of great significance to study the mechanism of interaction between martentoxin and BK channels. Methods: The three-dimensional structure of BK channel pore region was constructed by homologous modeling method, and the key amino acid sites of BK channel interaction with martentoxin were analyzed by protein-protein docking, molecular dynamic simulation and virtual alanine mutation. Results: Based on homologous modeling of BK channel pore structure and protein-protein docking analysis, Phe1, Lys28 and Arg35 of martentoxin were found to be key amino acids in toxin BK channel interaction. Conclusions: This study reveals the structural basis of martentoxin interaction with BK channel. These results will contribute to the design of BK channel specific blockers based on the structure of martentoxin.

Aberrant long non-coding RNA cancer susceptibility 15 (CASC15) plays a diagnostic biomarker and regulates inflammatory reaction in neonatal sepsis.

Neonatal sepsis (NS) is one of the important causes of neonatal death. There are many studies to confirm the role of long non-coding RNA (lncRNA) in neonatal infectious diseases. This study aimed to explore the level of cancer susceptibility 15 (CASC15) and its effect on inflammatory response in NS. Seventy-nine neonatal pneumonia (NP) patients and 80 NS patients were enrolled in this study. Reverse Transcription-quantitative PCR (RT-qPCR) was used to determine the expression levels of CASC15 and miR-144-3p. Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of CASC15 in NS. RAW264.7 cells were stimulated with LPS to simulate the inflammatory response in NS patients, and the regulation and mechanism of CASC15 on the inflammatory response were explored in this in vitro cell model. Serum CASC15 was upregulated in NS patients, and it had the ability to distinguish NS patients from NP patients. LPS stimulation increased the expression of CASC15 and simultaneously stimulated the secretion of inflammatory cytokines, while the knockdown of CASC15 alleviated the inflammatory response induced by LPS stimulation. Besides, serum miR-144-3p was reduced in NS patients, and luciferase reporter genes showed that miR-144-3p was a direct target of CASC15. Overexpression of CASC15 may promote the inflammatory response of NS by targeted regulating the expression of miR-144-3p, which may provide us with new insights in the treatment of NS.

Infrared spectroscopic imaging study of BV-2 microglia altering tumor cell biological activity and cellular fraction.

Tumor brain metastasis is a severe threat to patients' neurological function, in which microglia may be involved in the process of tumor cell metastasis among nerve cells. Our study focused on the interaction between microglia and breast and lung cancer cells. Changes in the proliferation and migration ability of cocultured tumor cells were examined; synchrotron radiation-based fourier transform infrared microspectroscopy (SR-FTIR) was used to detect changes in the structures and contents of biomolecules within the tumor cells. The experimental results showed that the proliferation and migration ability of tumor cells increased after coculture, and the structures and contents of biological macromolecules in tumor cells changed. The absorption peak positions of the amide Ⅱ and amide Ⅰ bands observed for the four kinds of tumor cells changed, and the absorption intensities were significantly enhanced, indicating changes in the secondary structures and contents of proteins in tumor cells, which may be the root cause of the change in tumor cell characteristics. Therefore, the metabolites of microglia may be involved in the progression of tumor cells in the nervous system. In this study, we focused on the interaction between microglia and tumor cells by using SR-FTIR and provided a new understanding of the mechanism of brain metastasis.

Stress-related hormone reduces autophagy through the regulation of phosphatidylethanolamine in breast cancer cells.

BACKGROUND: An increasing number of studies indicate that adrenergic signaling plays a fundamental role in tumor progression and metastasis induced by chronic stress. However, despite the growing attention, an understanding of the mechanisms linking chronic stress and cancer is still insufficient. METHODS: Western blot analysis and transmission electron microscopy (TEM) were used to observe the changes in autophagy level in a breast cancer cell line (MCF-7) after epinephrine treatment. Non-targeted metabolomics was also used to detect MCF-7 metabolites after epinephrine treatment. The xenograft model was used to detect the level of autophagy after epinephrine intervention. RESULTS: The results showed that epinephrine treatment reduced the autophagy level of breast cancer cells. Epinephrine changed the level of phosphatidylethanolamine (PE) in breast cancer cells as detected by non-targeted metabolomics. Epinephrine also changed autophagy in breast cancer cells by decreasing the level of PE in cells. When autophagy decreased, the invasion and migration of breast cancer cells increased in vitro, and the progression of breast cancer accelerated in vivo. CONCLUSIONS: These findings suggest that stress-related hormones affect the tumor progression of breast cancer. Therefore, strengthening the emotional management strategies of patients during the process of antitumor treatment as a supplement to the existing treatments may be beneficial.

Analysis of Pathogen Distribution and Its Antimicrobial Resistance in Bloodstream Infections in Hospitalized Children in East China, 2015-2018.

This study analyzed the pathogen distribution in bloodstream-infected (BSI) children hospitalized in Shandong Province from 2015 to 2018, to identify prevention strategies and select empiric antimicrobial therapy for BSI in children. Blood sample data from 14 107 children from 162 hospitals of Shandong Province were obtained from the China Antimicrobial Resistance Surveillance System and analyzed with WHONET 5.6 software. The results of the blood culture test showed the growth of 70.6% Gram-positive and 29.4% Gram-negative bacteria. Of the 14 107 blood isolates, 59.3% were collected from males and 40.7% were from females. Coagulase-negative staphylococci (47.1%) were the most commonly distributed pathogens. The distribution of pathogens varied according to age group and season. All Staphylococcus isolates were susceptible to vancomycin, teicoplanin and linezolid. Clinically, significant declines in penicillin-resistant Streptococcus pneumonia and carbapenem-resistant Escherichia coli were observed during the study period; however, detection rates of carbapenem-resistant Klebsiella pneumoniae increased over time (p < 0.05). Empiric antimicrobial therapy should be prescribed according to corresponding regional pediatric antimicrobial-resistant data.

Application of data mining in the provision of in-home medical care for patients with advanced cancer.

BACKGROUND: As the number of patients with cancer rises, home care for patients with advanced disease is becoming increasingly important. To provide guidance for home medical services and hospice care, we investigated the basic information and medical service information of patients with advanced cancer receiving home care by using a data mining algorithm to predict the patients' survival and medical expenses. METHODS: Data from patients with advanced cancer who received home care in Chongming District (Shanghai, China) between 2016 and 2018 were collected. The medical expenses and survival time of the patients were classified and predicted through the use of random forest algorithms, support-vector machine algorithms, and back-propagation (BP) neural network algorithms. RESULTS: The performances of the 3 algorithms in classifying patient survival and predicting medical expenses were compared. The random forest algorithm, support vector machine, and BP neural network in the classification of patient survival had accuracy of 81.94%±6.12%, 74.61%±7.01%, and 72.90%±8.08%, respectively. The standard mean square errors of the regression model for predicting medical expenses were 0.4194±0.2393, 1.1222±0.0648, and 1.2986±0.1762, respectively. CONCLUSIONS: The random forest algorithm is the most suitable prediction model for predicting medical costs and patient survival with the quantity of data currently available. Further optimization of the random forest algorithm could provide guidance and help medical institutions improve the efficiency and quality of home medical services for patients with advanced cancer.

Pain May Promote Tumor Progression via Substance P-Dependent Modulation of Toll-like Receptor-4.

BACKGROUND: In a previous study, persistent pain was suggested to be a risk factor for tumor patients. However, the mechanism underlying this phenomenon is still unclear. Substance P (SP), a pain-related neuropeptide secreted by the neural system and the immune system, plays an important role in the induction and maintenance of persistent pain. METHODS: In this study, in order to explore whether SP participates in the influence of pain on tumor progression, the serum samples of lung cancer and breast cancer patients were collected and tested. An elevated expression of SP was found in patients with pain. RESULTS: Cell pharmacological experiments revealed that SP can upregulate the expression of Toll-like receptor-4 (TLR-4) in tumor cells and increase the proliferation, migration, and invasive activity of tumor cells. As high expression of TLR-4 has the ability to enhance the biological activity of tumor cells, TLR-4 is thought to be involved in SP-induced tumor proliferation, migration, and invasion. Treatment of tumor cells with Aprepitant, a specific blocker of the NK-1 receptor, could reduce the expression of TLR-4 and reduce the proliferation, invasion, and migration activities of tumor cells; further proof of the influence of SP on TLR-4 expression depends on the NK-1 receptor located in tumor cells. CONCLUSIONS: Based on the results above, we proposed a possible mechanism underlying pain affecting tumor progression: The presence of pain increases the content of SP in patients' blood, and elevated SP increases the expression of tumor TLR-4 by acting on the NK-1 receptor, which ultimately affects the biological activity of the tumor.

Overexpression of acid-sensing ion channel 1a (ASIC1a) promotes breast cancer cell proliferation, migration and invasion.

BACKGROUND: The microenvironment of various tumor tissues is acidic. Acid-sensing ion channels (ASICs) are a class of ligand-gated ion channels which are sensitive to extracellular protons and are often highly expressed in tumor tissues. Breast cancer, whose extracellular microenvironment is thought to be acidic, is the most common cancer type among females in the world. METHODS: Thirty breast cancer tissues and adjacent normal tissues of patients were collected from 2009 to 2015 at the Xinhua hospital affiliated to Shanghai Jiao Tong University School of Medicine. The expression of acid-sensing ion channel 1a (ASIC1a), a subtype of ASICs family, was detected by immunohistochemistry in breast cancer tissues, and the effect of ASIC1a on the physiological activity of tumor cells was analyzed in vitro and in vivo experiments. RESULTS: In this study, it was found that ASIC1a is highly expressed in the tissues of breast cancer patients. In vitro experiments revealed that down-regulation of ASIC1a by its antagonist PcTx-1 or ASIC1a siRNA could significantly weaken the migration, proliferation and invasion of tumor cells. In vivo studies, down-regulation or inhibition of the ASIC1a could inhibit breast tumor growth. CONCLUSIONS: The high expression of ASIC1a might be related to the enhanced biological activity of breast cancer cells. Whether ASIC1a is a potential therapeutic target for some types of breast cancer deserves further study.

Frequency offset estimation for nonlinear frequency division multiplexing with discrete spectrum modulation.

Although fruitful studies have been conducted on carrier frequency offset (CFO) estimations in linear coherent optical fiber communication systems, there are few studies on CFO estimations and recoveries in the systems based on the nonlinear Fourier transform (NFT). Although the CFO is originated from the linear frequency domain, it definitely has effects on nonlinear spectra, including the shift of the nonlinear frequency and the phase rotations of the scattering data, which are similar to its effects on linear spectra. This work indicates that it is feasible to estimate frequency offset (FO) by capturing symbol variations in the nonlinear frequency domain (NFD) rather than in the linear frequency domain; the latter was usually exploited in the literature. Based on a thorough investigation of the FO induced behavior that appears in a nonlinear frequency division multiplexing (NFDM) system, we proposed a nonlinear frequency domain estimation method aided by training symbols (TS) using an angle search algorithm after NFT operations at the receiver. The discussions in this paper prove that the proposed method is generally applicable to the NFDM systems regardless of whether using single or multiple eigenvalues. A performance comparison between the NFD method and the conventional method in the linear frequency domain is performed with different modulation formats for both single and multiple eigenvalue NFDM transmission systems. The analysis results show that the proposed method holds the better stability and estimation accuracy in contrast with the linear domain estimation method. The TS overhead can also be deduced dramatically, which implies better transmission efficiency. Therefore, the NFD method is more powerful for eigenvalue NFDM transmission systems, especially for the scenarios where high order modulation formats and multiple eigenvalues are utilized.